The aim of this proposal is to utilize a variety of both in vitro and in vivo techniques to gain insight into the mechanism which regulates gastrin secretion and biosynthesis. An organ culture preparation will be employed to investigate the local interaction of antral peptides in the regulation of gastrin release in vitro. Preliminary data suggests that release of somatostatin from neighboring D cells may have a direct, paracrine, inhibitory effect on gastrin release from the G cells. A technique to measure gastrin biosynthesis is presently being developed which will be used to monitor and quantitate the kinetics of gastrin biosynthesis in antral organ culture explants under a variety of in vitro conditions. Another in vitro system which will be utilized is an isolated enriched G cell preparation. This preparation will be used to further characterize the intracellular events associated with "stimulus secretion coupling" of gastrin release. An attempt will also be made to identify dietary constituents which stimulate medium and cellular gastrin levels using both intact animals and the isolated and enriched endocrine cell preparation.